黄体酮生物黏附缓释栓的体外评价方法研究

目的 建立黄体酮生物黏附缓释栓的体外评价方法.方法 采用自制的体外黏附时间测定装置和Setnikar-Fantelli 装置模拟阴道环境,测定栓剂的黏附时间、液化时间和药物滞留量;采用转篮法和HPLC法测定黄体酮生物黏附缓释栓中药物的体外释放度.结果 同批栓剂的黏附时间、液化时间和药物滞留量试验测得值的RSD均小于10%(n=6),表明自制装置的精密度符合要求;体外释放度方法学研究结果表明,辅料不干扰药物的测定;黄体酮在6.008~120.16 μg/mL范围内呈良好的线性关系;平均回收率为99.55%,RSD为0.83%(n=9);采用所建立的方法测得3批栓剂的黏附时间为(42.11±1.71) s,液化时间为(22.12±0.88) h,8 h药物总滞留量为(98.41±0.10)%,6 h的药物累积释放率接近100%,表明栓剂有适宜的黏附时间和液化时间,可使药物在阴道内滞留长达8 h以上,并缓慢释放药物.结论 所建立的体外评价方法可用于(缓释)栓剂的质量控制.

In vitro evaluation of progesterone bioadhesive sustained release suppositories

Objective To establish an in vitro evaluation method for progesterone bioadhesive sustained release suppositories.Methods The adhesive time,liquefaction time and drug retention were measured using the self-made in vitro adhesion time device and Setnikar-Fantelli device,which simulated vaginal environment.In vitro release of the drug was determined by Basket method and HPLC.Results The RSD values for the determination of adhesion time,liquefaction time and drug retention were less than 10% (n=6),indicating the precision of the instrument could meet the requirements.The results of in vitro release method showed that the determination was not interfered by the excipients.Progesterone showed a good linearity in the range of 6.008 ~120.16 μg/mL.The average recovery rate was 99.55% and the RSD was 0.83%.The adhesive time was (42.11±1.71) s,and the liquefaction time was (22.12±0.88) h,the total drug retention at 8 h was (98.41±0.10)%,and the drug cumulative release ratio was close to 100% in 6 hours.3 batches of suppository samples showed adhesive time and liquefaction time,which could keep the drug in vagina for more than 8 hours,and release slowly.Conclusion The established in vitro evaluation method could be used for the quality control of sustained release suppositories.